Multi-target pharmacology: possibilities and limitations of the "skeleton key approach" from a medicinal chemist perspective

被引:279
作者
Talevi, Alan [1 ]
机构
[1] Natl Univ La Plata, Fac Exact Sci, Med Chem, Dept Biol Sci, La Plata, Buenos Aires, Argentina
关键词
multi-target agents; lock and key paradigm; gene profile; drug resistance; drug repositioning; drug design; designed multiple ligands; TRYPANOSOMA-CRUZI ACTIVITY; DRUG DISCOVERY; COMBINATION THERAPY; SYSTEMS BIOLOGY; MAGIC BULLETS; SINGLE-TARGET; THERAPEUTICS; AMIODARONE; NETWORKS; EPILEPSY;
D O I
10.3389/fphar.2015.00205
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Multi-target drugs have raised considerable interest in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance issues. Prospective drug repositioning to treat comorbid conditions is an additional, overlooked application of multi-target ligands. While medicinal chemists usually rely on some version of the lock and key paradigm to design novel therapeutics, modern pharmacology recognizes that the mid- and long-term effects of a given drug on a biological system may depend not only on the specific ligand-target recognition events but also on the influence of the repeated administration of a drug on the cell gene signature. The design of multi-target agents usually imposes challenging restrictions on the topology or flexibility of the candidate drugs, which are briefly discussed in the present article. Finally, computational strategies to approach the identification of novel multi-target agents are overviewed.
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收藏
页数:7
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